BR112021014617A2 - ORODISPERSIBLE TABLET - Google Patents

Abstract

orodispersible tablet. The present invention is directed to a composition in the form of an orodispersible tablet comprising a non-steroidal anti-inflammatory drug (NSAID) and a taste masking agent, wherein the NSAID is uncoated and has an average particle size of less than 100 µm. The present invention is further directed to the use of malic acid as a flavor masking agent.

Description

ORODISPERSIBLE TABLET FIELD OF THE INVENTION

[001] The present invention relates to a tablet, in particular, an orodispersible tablet and a method for masking the taste of the active ingredients in the orodispersible tablet.

BACKGROUND OF THE INVENTION

[002] Orodispersible tablets are compressed tablets with a lower hardness than conventional tablets, so that they disintegrate in the mouth of the consumer. Although orodispersible tablets disintegrate in the mouth, absorption of the active substance may not be through the oral mucosa, but through the stomach or small intestine.

[003] Advantageously, therefore, orodispersible tablets can be taken without water to deliver the actives to the stomach. Such an administration mechanism is not only convenient, but can be beneficial when there may be difficulty in swallowing conventional tablets, such as in young children, the elderly, or very ill patients.

[004] However, some actives must be taste masked if they are included in an orodispersible tablet due to their bitter taste and/or "throat stutter", which is common to many medications. For example, ibuprofen is a well-known medication that produces an unpleasant burning sensation in the mouth and throat after ingestion.

[005] In the state of the art, several methods of masking the taste or attenuating the "throat lock" are known. US patent 8,496,969 describes the use of an ibuprofen coated particle to form a taste masked tablet. The taste masking agent comprises a combination of cellulose acetate, hypromellose phthalate and polysorbate-80 and is supplied as a solution in which the solvent is 90% acetone and 10% water. Prior to coating, the ibuprofen is granulated to a size of over 200 µm. The use of a coating can impact the release of ibuprofen. US patent 5,405,617 is directed to the use of a fatty or aliphatic acid ester to coat an active pharmaceutical ingredient. The aliphatic acid or ester is melted before coating the active ingredient. WO 2013/143688 describes a process wherein an active pharmaceutical ingredient is taste masked by melt extrusion with a suitable excipient. The excipient is selected from the group consisting of fatty acids, fatty acid salts or esters, glyceride esters, waxes, polyvinyl caprolactam-polyvinyl polyethylene glycol acetate graft copolymer or combinations thereof.

[006] However, these medications can also be difficult to taste masking using standard dosage forms as they dissolve quickly in saliva and reach the taste buds. In particular, drug substances that have a small particle size will have an increased surface area and, as a result, will come into contact with more taste receptors, making effective taste masking more challenging. In contrast, drug substances with a larger particle size will have a reduced surface area and, as a result, will come into contact with fewer taste receptors. Consequently, compositions containing drug substances that require taste masking will generally use drugs with a higher particle size to reduce the need for taste masking as a result of their lower surface area. Smaller particle size grades of NSAIDs such as ibuprofen are known to be particularly difficult to mask effectively and, as a result, are not used in current orodispersible products.

[007] However, it is highly desirable that orodispersible compositions exhibit a mouthfeel that is acceptable to a patient. Orodispersible compositions comprising a drug substance with a higher particle size generally have an unpleasant or undesirable "sandy" sensation when dissolved in the mouth.

[008] In addition, orodispersible tablets can often have a high friability and low hardness to ensure that they disintegrate as needed when placed in the oral cavity. However, it can be difficult to manufacture orodispersible tablets that have the required disintegration profile and the required hardness and friability to be a viable commercial product.

[009] It would therefore be desirable to have an orodispersible tablet that comprises an uncoated active pharmaceutical and has a "smooth" mouthfeel, but does not exhibit an unpleasant taste.

[0010] Taste masking of orodispersible compositions that comprise an uncoated active pharmaceutical and have a "smooth" mouthfeel may require a large amount of taste masking agent which can make the tablet size larger than acceptable for a consumer.

[0011] It would therefore also be desirable to have an orodispersible tablet that comprises an uncoated active pharmaceutical and has a "smooth" mouthfeel, but does not require the inclusion of a large amount of a taste masking agent.

SUMMARY OF THE INVENTION

[0012] In accordance with one aspect of the present invention, there is provided a composition in the form of an orodispersible tablet comprising a non-steroidal anti-inflammatory drug (NSAID) and a taste masking agent, wherein the NSAID is uncoated and has a lower average particle size of 100 µm.

[0013] The average particle size of uncoated NSAID can be less than 90 µm. The average particle size of the uncoated NSAID can be less than 80 µm. The average particle size of the uncoated NSAID can be less than 70 µm. The average particle size of the uncoated NSAID can be less than 60 µm. The average particle size of the uncoated NSAID can be greater than 10 µm. The average particle size of the uncoated NSAID can be greater than 20 µm. The average particle size of the uncoated NSAID can be greater than 30 µm. The average particle size of the uncoated NSAID can be greater than 40 µm.

[0014] The average particle size of uncoated NSAID can be 10 µm - 80 µm. The average particle size of the uncoated NSAID may preferably be 30 µm - 70 µm. The average particle size of the uncoated NSAID may more preferably be 40-60 µm. A more preferred average particle size is 50 µm.

[0015] Preferably, the taste masking agent does not comprise a cyclodextrin.

[0016] Typically, the dosage amount for a pharmaceutical active in the treatment of pain, inflammation or fever is in the range of 25 - 600 mg, more preferably 100 - 400 mg depending on the appropriate dose level of the active pharmaceutical agent. A preferred dosage amount is 200 mg. An especially preferred dosage amount for the composition of the present invention is 200 mg of ibuprofen. When derivatives are employed, normally precise unit dosages are chosen to give the equivalent NSAID doses given above.

[0017] The most preferred active agents are those used in the treatment of pain, particularly ibuprofen, flurbiprofen, ketoprofen, aspirin, paracetamol, codeine, naproxen, indomethacin, diclofenac and meloxicam. Especially preferred is ibuprofen and pharmaceutically acceptable salts or hydrates thereof.

[0018] The taste masking agent can be selected from the group consisting of ascorbic acid, monosodium citrate, fumaric acid, malic acid and combinations thereof. A preferred taste masking agent is malic acid.

[0019] The taste masking agent may be present at a level of up to 15%. The amount of taste masking agent may be at least 0.1%. The amount of taste masking agent may be at least 0.5%. The amount of taste masking agent may be at least 1%. The amount of taste masking agent may be at least 5%. The amount of taste masking agent can be at least 7%.

[0020] The amount of taste masking agent can be up to 10%. The amount of taste masking agent can be up to 9%. The amount of taste masking agent can be up to 2%. The amount of taste masking agent can be up to 1%.

[0021] When the taste masking agent is selected to be malic acid, the amount present can be 0.1 - 15%. Preferably, the amount may be from 5 to 10%. More preferably, the amount may be from 7 to 9%.

[0022] The weight ratio of the non-steroidal anti-inflammatory drug (NSAID) and the taste masking agent in the composition can be 1:1 - 8:1. A preferred ratio is 3:1 - 5:1. The most preferred ratio is 4:1 by weight.

[0023] For a composition of the present invention, i.e. an orodispersible tablet, the active ingredient will generally be combined with various excipients. In particular, the composition will generally comprise one or more lubricants, glidants, fillers, binders, disintegrants, diluents or bulking agents.

[0024] Typically, the composition may include additional flavoring agents. The flavoring agent can be any suitable flavor, such as orange, cherry, cola, grapefruit, raspberry, lemon, blackberry, apricot or a refreshing flavor.

[0025] The flavoring agent may be present at a level of up to 5%. The flavoring agent may be present at a level of 0.1% - 3%.

[0026] The composition may further include a sweetener. The sweetener may be selected from the group consisting of mannitol, sorbitol, isomalt, sodium saccharin, acesulfame potassium, sucralose, aspartame, monoammonium glycyrrhizinate, neohesperidin dihydrochalcone, thaumatin, neotame, cyclamates and mixtures thereof. A preferred sweetener is sucralose.

[0027] Preferred filling materials include celluloses, polysaccharides and their derivatives, sugar alcohols and saccharides.

[0028] Polysaccharides that may be used include starch, e.g. e., corn starch, cellulose, e.g. e., powdered cellulose and microcrystalline cellulose, water-insoluble modified starches, e.g. e., sodium carboxymethyl starch, water-insoluble cellulose derivatives, e.g. e., croscarmellose sodium (cross-linked sodium carboxymethyl cellulose), cross-linked polyvinylpyrrolidone, maltodextrin and alginic acid.

[0029] Another preferred form of filler is a saccharide. Suitable saccharides include, for example, sucrose, lactose and dextrose.

[0030] Another preferred form of filler is a sugar alcohol. Suitable sugar alcohols include, for example, sorbitol, mannitol and xylitol. Mannitol is especially preferred.

[0031] Typically, the filler may be present at a level of 20 to 70% by weight of the composition. More typically, the filler may be present at a level of 40 to 50% by weight of the composition. More typically, the filler may be present at a level of 42-47% by weight of the composition.

[0032] Particularly preferred binders are dicalcium phosphate, microcrystalline cellulose, e.g. e., the products sold as Avicel PH-101 and Avicel PH-102 (Avicel is a trademark) and lactose. A preferred binder is microcrystalline cellulose. Typically, the binder may be present at a level of from 2 to 25% by weight of the composition. More typically, the binder may be present at a level of from 5 to 15% by weight of the composition. More typically, the binder may be present at a level of 8 - 12% by weight of the composition.

[0033] The disintegrant has the effect of helping the orodispersible tablet to disintegrate in the oral cavity. In addition to croscarmellose sodium, examples of disintegrants include one or more of wheat starch, corn starch, potato starch, sodium starch glycollate, low-substituted hydroxypropyl cellulose, alginic acid, cross-linked polyvinylpyrrolidone (crospovidone) and magnesium aluminum silicate. . Preferred disintegrants are those that swell with water, thereby causing the orodispersible tablet ingredients to be pushed out and out of the aqueous disintegration medium. A preferred disintegrant is cross-linked polyvinylpyrrolidone (crospovidone). The disintegrant is present in a disintegrating effective amount, for example up to 20% by weight of the composition, more preferably 1-10% w/w, even more preferably 2-8% w/w and most preferably 3-6% by weight of the composition.

[0034] A particularly preferred composition includes a mixture of a cellulosic binder, a sugar alcohol filler and a disintegrant. The preferred cellulosic binder is microcrystalline cellulose, the preferred sugar alcohol is mannitol, and the preferred disintegrant is cross-linked polyvinylpyrrolidone (crospovidone).

[0035] Typically, the composition comprises the cellulosic binder, the sugar alcohol filler and the disintegrant in the proportion of 0.01 - 10 parts by weight of cellulosic binder: 0.01 - 10 parts by weight of sugar alcohol filler : 1 part by weight of disintegrant. More preferably, the composition contains 2-4 parts by weight of cellulosic binder per part by weight of disintegrant and 8-12 parts by weight of sugar alcohol filler per part by weight of disintegrant. More preferably, the composition contains cellulosic binder, sugar alcohol filler and disintegrant in a weight ratio of 2 - 3:11 - 12:1 parts by weight. Preferably,

the composition contains cellulosic binder, sugar alcohol filler and disintegrant in a weight ratio of 2.5:11.5:

1. Alternatively, the composition may contain cellulosic binder, sugar alcohol filler and disintegrant in a weight ratio of 2.5:11.4:1. Alternatively, the composition contains cellulosic binder, sugar alcohol filler and disintegrant in a weight ratio of 2.5:11.05:1.

[0036] The binder, filler and/or disintegrant are preferably incorporated into the composition in finely divided (powder) form.

[0037] The binder and filler preferably together constitute in excess of 40% w/w of the composition, more preferably in excess of 45% w/w, and most preferably in excess of 50% w/w. The binder and filler, preferably together, constitute less than 65% w/w of the composition, more preferably less than 70% w/w, and most preferably less than 75% w/w. The binder and filler, preferably together, constitute between 40 and 75% w/w of the composition, more preferably between 45 and 70% w/w, and most preferably between 50 and 65% w/w. Preferably, the binder and filler together constitute between 50 and 56% w/w of the composition. Alternatively, the binder and filler together may constitute between 60 - 65% w/w.

[0038] The lubricant may be, for example, stearic acid, a stearate, a fumarate or a polyethylene glycol of molecular weight of 4,000 or more. The preferred lubricant is a metal fumarate, particularly sodium stearyl fumarate, which lubricant may be present in the composition at low levels of up to 5%, typically than 1% or 3%, by weight, alone or in combination. Lubricant may be present at a level of 1.25%.

[0039] The glidant can be selected from the group consisting of silica, talc or starch. The slider is normally present at a level of up to 5%. The slider may be present at a level of 0.1% - 4%. The slider may be present at a level of 0.5% - 2%. The slider may be present at a level of 0.75% - 1.5%. The slider may be present at a level of 1%.

[0040] For the avoidance of doubt, in the context of the present application, a glidant is a component that ensures that the powder that forms the orodispersible tablet flows easily into the tablet press dies, and a lubricant is defined as a component that assists in the ejection of the orodispersible tablet from the press dies and prevents the orodispersible tablet from adhering to the punches.

[0041] The composition can have a friability of up to 2% w/p and a hardness between 40N and 100N. The composition may have a friability of less than 1% w/p and a hardness of more than 50N. The composition may have a friability of less than 1% w/p and a hardness of more than 60N. The composition may have a friability of less than 1% w/p and a hardness of more than 70N. The composition may have a friability of less than 1% w/p and a hardness of more than 80N. The composition may have a friability of less than 0.5% w/p and a hardness of greater than 50N. The composition may have a friability of less than 0.5% w/p and a hardness of greater than 60N. The composition may have a friability of less than 0.5% w/p and a hardness of more than 70N. The composition may have a friability of less than 0.5% w/p and a hardness of greater than 80N.

[0042] Preferably, the composition can have a friability of less than 1% w/p and a hardness greater than 80N. More preferably, the composition may have a friability of less than 0.5% w/p and a hardness of greater than 80N.

[0043] The composition may comprise an uncoated non-steroidal anti-inflammatory drug (NSAID), a taste masking agent and a disintegrant wherein the uncoated NSAID has an average particle size of less than 100 µm, the masking agent flavor is selected to be malic acid which may be present in an amount of 0.1-15% by weight of the composition, and the disintegrant is selected to be cross-linked polyvinylpyrrolidone (crospovidone) which may be present in an amount of 1-10 % by weight of the composition.

[0044] Typically, the amount of malic acid may be from 5 to 10% by weight of the composition. More typically, the amount of malic acid may be from 7 to 9% by weight of the composition.

[0045] Typically, the amount of crospovidone may be from 2 to 8% by weight of the composition and more typically from 3 to 6% by weight of the composition.

[0046] The composition may comprise an uncoated non-steroidal anti-inflammatory drug (NSAID), a taste masking agent and a disintegrant wherein the uncoated NSAID has an average particle size of less than 100 µm, the masking agent The flavor agent is selected to be malic acid which may be present in an amount of 0.1-15% by weight of the composition, wherein the ratio of the uncoated non-steroidal anti-inflammatory drug (NSAID) to the taste masking agent is 4:1 by weight. The average particle size of the uncoated NSAID can be from 40 to 60 µm. A preferred average particle size of the NSAID is 50 µm. Preferably, the uncoated non-steroidal anti-inflammatory drug (NSAID) is ibuprofen. Typically, the amount of malic acid may be from 5 to 10% by weight of the composition. More typically, the amount of malic acid may be from 7 to 9% by weight of the composition.

[0047] The composition may comprise an uncoated non-steroidal anti-inflammatory drug (NSAID), a taste masking agent and a disintegrant wherein the uncoated NSAID has an average particle size of less than 100 µm, the masking agent The flavor agent is selected to be malic acid which may be present in an amount of 0.1-15% by weight of the composition, wherein the ratio of the uncoated non-steroidal anti-inflammatory drug (NSAID) to the taste masking agent is 4:1 by weight and the disintegrant is selected to be cross-linked polyvinylpyrrolidone (crospovidone) which may be present in an amount of 1-10% by weight of the composition. The average particle size of the uncoated NSAID can be from 40 to 60 µm. A preferred average particle size of the NSAID is 50 µm. Preferably, the uncoated non-steroidal anti-inflammatory drug

(NSAID) is ibuprofen. Typically, the amount of malic acid may be from 5 to 10% by weight of the composition. More typically, the amount of malic acid may be from 7 to 9% by weight of the composition. Typically, the amount of crospovidone may be from 2 to 8% by weight of the composition and more typically from 3 to 6% by weight of the composition.

[0048] The composition may comprise uncoated non-steroidal anti-inflammatory drug (NSAID), a taste masking agent and a disintegrant wherein the uncoated NSAID has an average particle size of 50 µm, the taste masking agent is selected to be malic acid which may be present in an amount of 7 - 9% by weight of the composition, wherein the ratio of uncoated non-steroidal anti-inflammatory drug (NSAID) to taste masking agent is 4: 1 by weight and the disintegrant is selected to be cross-linked polyvinylpyrrolidone (crospovidone) which may be present in an amount of 3 to 6% by weight of the composition.

[0049] The composition may further comprise 0.1% - 2% w/w of a coloring agent.

[0050] The composition may comprise uncoated ibuprofen, a taste masking agent and a disintegrant, wherein the uncoated ibuprofen has an average particle size of less than 100 µm, and, wherein the weight ratio of ibuprofen: agent of taste masking: disintegrant is about 10:5:1 to about 5:1:1. Typically, the composition may comprise uncoated ibuprofen, a taste masking agent and a disintegrant, wherein the weight ratio of ibuprofen:

taste masking agent: disintegrant is about 8:2:1 to about 7:1:1.

[0051] The composition may comprise uncoated ibuprofen, a taste masking agent and a disintegrant, wherein the uncoated ibuprofen has an average particle size of less than 100 µm, the taste masking agent is selected to be malic acid which may be present in an amount of 0.1 - 15% by weight of the composition, wherein the ratio of uncoated ibuprofen to taste masking agent is 4:1 by weight and the disintegrant is selected to be cross-linked polyvinylpyrrolidone ( crospovidone) which may be present in an amount of 1 - 10% by weight of the composition and wherein the weight ratio of ibuprofen:malic acid: crosslinked polyvinylpyrrolidone is from about 10:5:1 to about 5:1:1 . The average particle size of uncoated ibuprofen can be from 40 to 60 µm. A preferred average particle size of the NSAID is 50 µm. Typically, the weight ratio of uncoated ibuprofen, malic acid, cross-linked polyvinylpyrrolidone is from about 8:2:1 to about 7:1:1.

[0052] The composition may comprise uncoated ibuprofen, a taste masking agent and a disintegrant wherein the uncoated ibuprofen has an average particle size of 50 µm, the taste masking agent is selected to be malic acid which can be present in an amount of 7 - 9% by weight of the composition, wherein the ratio of uncoated ibuprofen to taste masking agent is 4:1 by weight and the disintegrant is selected to be cross-linked polyvinylpyrrolidone (crospovidone) which can being present in an amount of 3 - 6% by weight of the composition and wherein the weight ratio of ibuprofen: taste masking agent: disintegrant is from about 8:2:1 to about 7:1:1.

[0053] The composition may comprise an uncoated non-steroidal anti-inflammatory drug (NSAID), a taste masking agent, a binder, a disintegrant and a filler wherein the uncoated NSAID has an average particle size of less than 100 µm, the taste masking agent may be present in an amount of 0.1 - 15% by weight of the composition, wherein the ratio of NSAID to taste masking agent is 4:1 by weight, and wherein the composition contains 2 - 4 parts by weight of binder per part by weight of disintegrant and 8 - 12 parts by weight of filler per part by weight of disintegrant. The average particle size of the uncoated NSAID can be from 40 to 60 µm. A preferred average particle size of the NSAID is 50 µm. Preferably, the uncoated non-steroidal anti-inflammatory drug (NSAID) is ibuprofen. Typically, the amount of taste masking agent may be from 5 to 10% by weight of the composition. More typically, the amount of taste masking agent may be from 7 to 9% by weight of the composition.

[0054] The composition may comprise an uncoated non-steroidal anti-inflammatory drug (NSAID), a taste masking agent, a cellulosic binder, a disintegrant and a sugar alcohol filler wherein the uncoated NSAID is of average size. of particle size less than 100 µm, the taste masking agent is selected to be malic acid which may be present in an amount of 0.1 - 15% by weight of the composition, wherein the ratio of the NSAID to the taste masking agent taste is 4:1 by weight and wherein the composition contains 2 - 4 parts by weight of cellulosic binder per part by weight of disintegrant and 8 - 12 parts by weight of sugar alcohol filler per part by weight of disintegrant . The average particle size of the uncoated NSAID can be from 40 to 60 µm. A preferred average particle size of the NSAID is 50 µm. Preferably, the uncoated non-steroidal anti-inflammatory drug (NSAID) is ibuprofen. Typically, the amount of malic acid may be from 5 to 10% by weight of the composition. More typically, the amount of malic acid may be from 7 to 9% by weight of the composition.

[0055] The composition may comprise an uncoated non-steroidal anti-inflammatory drug (NSAID), a taste masking agent and a disintegrant wherein the uncoated NSAID has an average particle size of less than 100 µm, the masking agent The flavor agent is selected to be malic acid which may be present in an amount of 0.1 - 15% by weight of the composition, wherein the ratio of the uncoated non-steroidal anti-inflammatory drug (NSAID) to the taste masking agent is 4:1 by weight and the disintegrant is selected to be cross-linked polyvinylpyrrolidone (crospovidone) which may be present in an amount of 1 - 10% by weight of the composition. The average particle size of the uncoated NSAID can be from 40 to 60 µm. A preferred average particle size of the NSAID is 50 µm. Preferably, the uncoated non-steroidal anti-inflammatory drug (NSAID) is ibuprofen. Typically, the amount of malic acid may be from 5 to 10% by weight of the composition. More typically, the amount of malic acid may be from 7 to 9% by weight of the composition. Typically, the amount of crospovidone may be from 2 to 8% by weight of the composition and more typically from 3 to 6% by weight of the composition.

[0056] The composition may be in the form of an orodispersible tablet comprising uncoated ibuprofen, a taste masking agent, a cellulosic binder, a disintegrant and a sugar alcohol filler wherein the ibuprofen has an average particle size of 50 µm, the taste masking agent is selected to be malic acid and is present in an amount of 0.1 - 15% by weight of the composition, wherein the ratio of uncoated ibuprofen to taste masking agent is 4: 1 by weight, the cellulosic binder is selected to be microcrystalline cellulose and is present in an amount of 2 to 25% by weight of the composition, the disintegrant is selected to be cross-linked polyvinylpyrrolidone (crospovidone) and is present in an amount of 1-10 % by weight of the composition, the filler is selected to be mannitol and is present in an amount of 20 to 70% by weight of the composition, wherein the composition contains 2 to 4 parts by weight of cellulosic binder o per part by weight of disintegrant and 8 - 12 parts by weight of sugar alcohol filler per part by weight of disintegrant, and wherein the weight ratio of ibuprofen:malic acid:

Cross-linked polyvinylpyrrolidone is from about 10:5:1 to about 5:1:1.

[0057] Typically, the amount of malic acid may be from 5 to 10% by weight of the composition. More typically, the amount of malic acid may be from 7 to 9% by weight of the composition. Typically, microcrystalline cellulose may be present at a level of 5 to 15% by weight of the composition. More typically, microcrystalline cellulose may be present at a level of 8 - 12% by weight of the composition. Typically, the amount of crospovidone may be from 2 to 8% by weight of the composition. More typically, the amount of crospovidone may be from 3 to 6% by weight of the composition. Typically, mannitol may be present at a level of 40-50% by weight of the composition. More typically, the mannitol may be present at a level of 42-47% by weight of the composition. The composition may contain cellulosic binder, sugar alcohol filler and disintegrant in a weight ratio of 2 - 3:11 - 12:1 parts by weight. Typically, the weight ratio of ibuprofen: malic acid: cross-linked polyvinylpyrrolidone is from about 8:2:1 to about 7:1:1.

[0058] Preferably, the composition may be in the form of an orodispersible tablet comprising uncoated ibuprofen, a taste masking agent, a cellulosic binder, a disintegrant and a sugar alcohol filler wherein the ibuprofen has an average size of 50 µm particle, taste masking agent is selected to be malic acid and is present in an amount of 7 - 9% by weight of the composition, wherein the ratio of NSAID to taste masking agent is 4:1 by weight , the cellulosic binder is selected to be microcrystalline cellulose and is present in an amount of 8 to 12% by weight of the composition, the disintegrant is selected to be cross-linked polyvinylpyrrolidone (crospovidone) and is present in an amount of 3 to 6% by weight of the composition, the filler is selected to be mannitol and is present in an amount of 42-47% by weight of the composition, cellulosic binder, sugar alcohol filler and disintegrant in a weight ratio of 2 - 3:11 - 12:1 parts by weight, and wherein the weight ratio of ibuprofen: malic acid: cross-linked polyvinylpyrrolidone is from about 8:2:1 to about 7:1: 1.

The composition may comprise: (a) 20 - 35% of an uncoated NSAID having an average particle size of less than 100 µm or a pharmaceutically acceptable salt thereof; (b) 20 - 70% of a filler; (c) 0.5 - 5% of a lubricant; (d) 5 - 10% of a taste masking agent; and (e) 1 - 10% of a disintegrant.

[0060] The average particle size of uncoated NSAID can be 40 to 60 µm. A preferred average particle size of the uncoated NSAID is 50 µm.

[0061] The composition typically further comprises one or more additional excipients selected from: (a) 0.1 - 5% of a glidant; and (b) 2 - 25% of a binder.

[0062] The composition may comprise:

(a) 25 - 30% of an uncoated NSAID having an average particle size of less than 100 µm or a pharmaceutically acceptable salt thereof; (b) 40 - 50% of a filler; (c) 0.5 - 5% of a lubricant; (d) 5 - 10% of a taste masking agent; and (e) 1 - 10% of a disintegrant.

[0063] The average particle size of the uncoated NSAID can be from 40 to 60 µm. A preferred average particle size of the uncoated NSAID is 50 µm.

[0064] The composition typically further comprises one or more additional excipients selected from: (a) 0.1 - 5% of a glidant; and (b) 2 - 25% of a binder.

[0065] Alternatively, the composition may comprise: (a) 20 - 35% of an uncoated NSAID having an average particle size of less than 100 µm or a pharmaceutically acceptable salt thereof; (b) 0.1 - 5% of a glidant; (c) 20 - 70% of a filler; (d) 0.5 - 5% of a lubricant; (e) 2 - 25% of a binder; (f) 5 - 10% of a taste masking agent; and (g) 1 - 10% of a disintegrant.

[0066] The average particle size of the uncoated NSAID can be 40 to 60 µm. A preferred average particle size of the uncoated NSAID is 50 µm.

[0067] The composition may comprise:

(a) 25 - 30% of an uncoated NSAID having an average particle size of less than 100 µm or a pharmaceutically acceptable salt thereof; (b) 0.1 - 5% of a glidant; (c) 40 - 50% of a filler; (d) 0.5 - 5% of a lubricant; (e) 5 - 15% of a binder; (f) 5 - 10% of a taste masking agent; and (g) 1 - 10% of a disintegrant.

[0068] The average particle size of uncoated NSAID can be 40 to 60 µm. A preferred average particle size of the uncoated NSAID is 50 µm.

[0069] The composition may comprise: (a) 28 - 30% of an uncoated NSAID having an average particle size of less than 100 µm or a pharmaceutically acceptable salt thereof; (b) 0.5 - 1.5% of a glidant; (c) 42 - 47% of a filler; (d) 0.75 - 1.5% of a lubricant; (e) 8 - 12% of a binder; (f) 6 - 8% of a taste masking agent; and (g) 3 - 5% of a disintegrant.

[0070] The average particle size of the uncoated NSAID can be 40 to 60 µm. A preferred average particle size of the uncoated NSAID is 50 µm.

[0071] The composition may comprise: (a) 25 - 30% uncoated ibuprofen having an average particle size of less than 100 µm or a pharmaceutically acceptable salt thereof;

(b) 0.1 - 5% colloidal silica; (c) 40 - 50% mannitol; (d) 0.5 - 5% sodium stearyl fumarate; (e) 5 - 15% microcrystalline cellulose; (f) 5 - 10% malic acid; and (g) 1 - 10% crospovidone.

[0072] The average particle size of uncoated ibuprofen can be 40 to 60 µm. A preferred average particle size of uncoated ibuprofen is 50 µm.

[0073] The composition may more preferably comprise: (a) 28 - 30% uncoated ibuprofen having an average particle size of less than 100 µm or a pharmaceutically acceptable salt thereof; (b) 0.5 - 1.5% of a colloidal silica; (c) 42-47% of a mannitol; (d) 0.75 - 1.5% of a sodium stearyl fumarate; (e) 8 - 12% of a microcrystalline cellulose; (f) 6 - 8% of a malic acid; and (g) 3 - 5% of a crospovidone.

[0074] The average particle size of uncoated ibuprofen can be 40 to 60 µm. A preferred average particle size of uncoated ibuprofen is 50 µm.

[0075] The composition may consist essentially of an uncoated non-steroidal anti-inflammatory drug (NSAID), a taste masking agent and a disintegrant wherein the uncoated NSAID has an average particle size of less than 100 µm, the agent The taste masking agent is selected to be malic acid which may be present in an amount of 0.1-15% by weight of the composition, wherein the ratio of the uncoated non-steroidal anti-inflammatory drug (NSAID) to the masking agent of flavor is 4:1 by weight. The average particle size of the uncoated NSAID can be from 40 to 60 µm. A preferred average particle size of the NSAID is 50 µm. Typically, the uncoated NSAID is selected to be ibuprofen. Typically, the amount of malic acid may be from 5 to 10% by weight of the composition. More typically, the amount of malic acid may be from 7 to 9% by weight of the composition. Typically, the disintegrant is selected to be crospovidone which is present in an amount of 2 to 8% by weight of the composition. More typically, the crospovidone is present in an amount of 3 to 6% by weight of the composition. Typically, the weight ratio of ibuprofen: malic acid: cross-linked polyvinylpyrrolidone is from about 8:2:1 to about 7:1:1.

[0076] More typically, the binder may be present at a level of 40 to 50% by weight of the composition. More typically, the binder may be present at a level of 42-47% by weight of the composition.

[0077] The composition may contain cellulosic binder, sugar alcohol filler and disintegrant in a weight ratio of 2 - 3:11 - 12:1 parts by weight.

[0078] The composition may consist essentially of an uncoated non-steroidal anti-inflammatory drug (NSAID), a taste masking agent and a disintegrant wherein the uncoated NSAID has an average particle size of less than 100 µm, the agent The taste masking agent is selected to be malic acid which may be present in an amount of 0.1-15% by weight of the composition, wherein the ratio of the uncoated non-steroidal anti-inflammatory drug (NSAID) to the masking agent of flavor is 4:1 by weight and the disintegrant is selected to be cross-linked polyvinylpyrrolidone (crospovidone) which may be present in an amount of 1-10% by weight of the composition. The average particle size of the uncoated NSAID can be from 40 to 60 µm. A preferred average particle size of the NSAID is 50 µm. Typically, the uncoated NSAID is selected to be ibuprofen.

[0079] The composition may consist essentially of an uncoated non-steroidal anti-inflammatory drug (NSAID), a taste masking agent and a disintegrant wherein the uncoated NSAID has an average particle size of less than 100 µm, the agent The taste masking agent is selected to be malic acid which may be present in an amount of 0.1-15% by weight of the composition, wherein the ratio of the uncoated non-steroidal anti-inflammatory drug (NSAID) to the masking agent of flavor is 4:1 by weight and the disintegrant is selected to be cross-linked polyvinylpyrrolidone (crospovidone) which may be present in an amount of 1-10% by weight of the composition. The average particle size of the uncoated NSAID can be from 40 to 60 µm. A preferred average particle size of the NSAID is 50 µm. Typically, the uncoated NSAID is selected to be ibuprofen.

[0080] Preferably, the composition can have a friability of less than 1% w/p and a hardness greater than 80N. More preferably, the composition may have a friability of less than 0.5% w/p and a hardness of greater than 80N.

[0081] The composition may be in the form of an orodispersible tablet consisting essentially of uncoated ibuprofen, a taste masking agent, a cellulosic binder, a disintegrant and a sugar alcohol filler wherein the ibuprofen has an average particle size of 50 µm, the taste masking agent is selected to be malic acid and is present in an amount of 7 - 9% by weight of the composition, wherein the ratio of NSAID to taste masking agent is 4:1 by weight, the cellulosic binder is selected to be microcrystalline cellulose and is present in an amount of 8 to 12% by weight of the composition, the disintegrant is selected to be cross-linked polyvinylpyrrolidone (crospovidone) and is present in an amount of 3 to 6% by weight of the composition. composition, the filler is selected to be mannitol and is present in an amount of 42-47% by weight of the composition, cellulosic binder, sugar alcohol filler and disintegrant in a weight ratio of 2 - 3:11 - 12:1 parts by weight, and, wherein the weight ratio of ibuprofen:malic acid: crosslinked polyvinylpyrrolidone is from about 8:2:1 to about 7:1: 1.

[0082] The composition may be in the form of an orodispersible tablet consisting essentially of uncoated ibuprofen, a taste masking agent,

a cellulosic binder, a disintegrant and a sugar alcohol filler wherein ibuprofen has an average particle size of 50 µm, taste masking agent is selected to be malic acid and is present in an amount of 7 - 9% by weight of the composition, wherein the ratio of NSAID to taste masking agent is 4:1 by weight, the cellulosic binder is selected to be microcrystalline cellulose and is present in an amount of 8 to 12% by weight of the composition, the disintegrant is selected to be cross-linked polyvinylpyrrolidone (crospovidone) and is present in an amount of 3 to 6% by weight of the composition, the filler is selected to be mannitol and is present in an amount of 42-47% by weight of the composition, cellulosic binder , sugar alcohol filler and disintegrant in a weight ratio of 2 - 3:11 - 12:1 parts by weight, and wherein the weight ratio of ibuprofen: malic acid: cross-linked polyvinylpyrrolidone is about 8:2:1 to about 7:1:1 and wherein the composition has a friability of less than 0.5% w/p and a hardness of greater than 80N.

[0083] The composition may consist essentially of: (a) 20 - 35% of an uncoated NSAID having an average particle size of less than 100 µm or a pharmaceutically acceptable salt thereof; (b) 5 - 10% of a taste masking agent; (c) 1 - 10% of a disintegrant; and (d) 2 - 25% of a binder.

[0084] The average particle size of uncoated NSAID can be 40 to 60 µm. A preferred average particle size of the uncoated NSAID is 50 µm. The composition may further include one or more from 20 to 70% filler, 0.5 to 5% lubricant and 0.1 to 5% glidant.

[0085] The composition may consist essentially of: (a) 25 - 30% of an uncoated NSAID having an average particle size of less than 100 µm or a pharmaceutically acceptable salt thereof; (b) 5 - 10% of a taste masking agent; (c) 1 - 10% of a disintegrant; and (d) 2 - 25% of a binder.

[0086] The average particle size of uncoated NSAID can be from 40 to 60 µm. A preferred average particle size of the uncoated NSAID is 50 µm. The composition may further include one or more from 40 to 50% filler, 0.5 to 5% lubricant and 0.1 to 5% glidant.

[0087] The composition may consist essentially of: (a) 25 - 30% of an uncoated NSAID having an average particle size of less than 100 µm or a pharmaceutically acceptable salt thereof; (b) 5 - 10% of a taste masking agent; (c) 1 - 10% of a disintegrant; and (d) 5 - 15% of a binder.

[0088] The average particle size of uncoated NSAID can be 40 to 60 µm. A preferred average particle size of the uncoated NSAID is 50 µm. The composition may further include one or more from 40 to 50% filler, 0.5 to 5% lubricant and 0.1 to 5% glidant.

[0089] The composition may consist essentially of: (a) 28 - 30% of an uncoated NSAID having an average particle size of less than 100 µm or a pharmaceutically acceptable salt thereof; (b) 6 - 8% of a taste masking agent; (c) 3 - 5% of a disintegrant; and (d) 8 - 12% of a binder.

[0090] The average particle size of uncoated NSAID can be 40 to 60 µm. A preferred average particle size of the uncoated NSAID is 50 µm. The composition may further include one or more of 42 - 47% filler, 0.75 - 1.5% lubricant and 0.5 - 1.5% glidant.

[0091] The composition may consist essentially of: (a) 25 - 30% uncoated ibuprofen with an average particle size of less than 100 µm or a pharmaceutically acceptable salt thereof; (b) 5 - 15% microcrystalline cellulose; (c) 5 - 10% malic acid; and (d) 1 - 10% crospovidone.

[0092] The average particle size of uncoated ibuprofen can be 40 to 60 µm. A preferred average particle size of uncoated ibuprofen is 50 µm. The composition may further include one or more than 0.1 - 5% colloidal silica, 40 - 50% mannitol and 0.5 - 5% sodium stearyl fumarate.

[0093] The composition may consist essentially of: (a) 28 - 30% uncoated ibuprofen with an average particle size of less than 100 µm or a pharmaceutically acceptable salt thereof; (b) 8 - 12% microcrystalline cellulose; (c) 6 - 8% malic acid; and (d) 3 - 5% crospovidone.

[0094] The average particle size of uncoated ibuprofen can be 40 to 60 µm. A preferred average particle size of uncoated ibuprofen is 50 µm. The composition may further include one or more of 0.5-1.5% colloidal silica, 42-47% mannitol and 0.75-1.5% sodium stearyl fumarate.

[0095] The composition may consist essentially of: (a) 20 - 35% of an uncoated NSAID having an average particle size of less than 100 µm or a pharmaceutically acceptable salt thereof; (b) 20 - 70% of a filler; (c) 0.5 - 5% of a lubricant; (d) 5 - 10% of a taste masking agent; (e) 1 - 10% of a disintegrant; and (f) 2 - 25% of a binder.

[0096] The average particle size of uncoated NSAID can be from 40 to 60 µm. A preferred average particle size of the uncoated NSAID is 50 µm. The composition may further include 0.1 - 5% of a glidant.

[0097] The composition may consist essentially of: (a) 25 - 30% of an uncoated NSAID having an average particle size of less than 100 µm or a pharmaceutically acceptable salt thereof; (b) 40 - 50% of a filler; (c) 0.5 - 5% of a lubricant; (d) 5 - 10% of a taste masking agent; (e) 1 - 10% of a disintegrant; and (f) 2 - 25% of a binder.

[0098] The average particle size of uncoated NSAID can be 40 to 60 µm. A preferred average particle size of the uncoated NSAID is 50 µm. The composition may further include 0.1 - 5% of a glidant.

[0099] The composition may consist essentially of: (a) 20 - 35% of an NSAID having an average particle size of less than 100 µm or a pharmaceutically acceptable salt thereof; (b) 0.1 - 5% of a glidant; (c) 20 - 70% of a filler; (d) 0.5 - 5% of a lubricant; (e) 2 - 25% of a binder; (f) 5 - 10% of a taste masking agent; and (g) 1 - 10% of a disintegrant.

[00100] The average particle size of uncoated NSAID can be 40 to 60 µm. A preferred average particle size of the uncoated NSAID is 50 µm.

[00101] The composition may consist essentially of: (a) 25 - 30% of an uncoated NSAID having an average particle size of less than 100 µm or a pharmaceutically acceptable salt thereof; (b) 0.1 - 5% of a glidant; (c) 40 - 50% of a filler; (d) 0.5 - 5% of a lubricant; (e) 5 - 15% of a binder; (f) 5 - 10% of a taste masking agent; and (g) 1 - 10% of a disintegrant.

[00102] The average particle size of the uncoated NSAID can be 40 to 60 µm. A preferred average particle size of the uncoated NSAID is 50 µm.

[00103] The composition may consist essentially of: (a) 28 - 30% of an uncoated NSAID having an average particle size of less than 100 µm or a pharmaceutically acceptable salt thereof; (b) 0.5 - 1.5% of a glidant; (c) 42 - 47% of a filler; (d) 0.75 - 1.5% of a lubricant; (e) 8 - 12% of a binder; (f) 6 - 8% of a taste masking agent; and (g) 3 - 5% of a disintegrant.

[00104] The average particle size of uncoated NSAID can be 40 to 60 µm. A preferred average particle size of the uncoated NSAID is 50 µm.

[00105] The composition may consist essentially of: (a) 25 - 30% uncoated ibuprofen with an average particle size of less than 100 µm or a pharmaceutically acceptable salt thereof; (b) 0.1 - 5% colloidal silica; (c) 40 - 50% mannitol; (d) 0.5 - 5% sodium stearyl fumarate; (e) 5 - 15% microcrystalline cellulose; (f) 5 - 10% malic acid; and (g) 1 - 10% crospovidone.

[00106] The average particle size of uncoated ibuprofen can be 40 to 60 µm. A preferred average particle size of uncoated ibuprofen is 50 µm.

[00107] The composition may consist essentially of: (a) 28 - 30% uncoated ibuprofen with an average particle size of less than 100 µm or a pharmaceutically acceptable salt thereof; (b) 0.5 - 1.5% of a colloidal silica; (c) 42-47% of a mannitol; (d) 0.75 - 1.5% of a sodium stearyl fumarate; (e) 8 - 12% of a microcrystalline cellulose; (f) 6 - 8% of a malic acid; and (g) 3 - 5% of a crospovidone.

[00108] The average particle size of uncoated ibuprofen can be from 40 to 60 µm. A preferred average particle size of uncoated ibuprofen is 50 µm.

[00109] The composition of the present invention may have a friability of up to 2% w/w and a hardness between 40N and 100N. The composition of the present invention may have a friability of less than 1% w/p and a hardness of greater than 50N. The composition of the present invention may have a friability of less than 1% w/p and a hardness of greater than 60N. The composition of the present invention may have a friability of less than 1% w/p and a hardness of greater than 70N. The composition of the present invention may have a friability of less than 1% w/p and a hardness of greater than 80N. The composition of the present invention may have a friability of less than 0.5% w/p and a hardness of greater than 50N. The composition of the present invention may have a friability of less than 0.5% w/p and a hardness of greater than 60N. The composition of the present invention may have a friability of less than 0.5% w/p and a hardness of greater than 70N. The composition of the present invention may have a friability of less than 0.5% w/p and a hardness of greater than 80N.

[00110] Preferably, the composition of the present invention may have a friability of less than 1% w/p and a hardness of greater than 80N. More preferably, the composition of the present invention may have a friability of less than 0.5% w/p and a hardness of greater than 80N.

[00111] Preferably, the composition may consist essentially of: (a) 25 - 30% of an uncoated NSAID having an average particle size of 50 µm or a pharmaceutically acceptable salt thereof; (b) 40 - 50% of a filler; (c) 0.5 - 5% of a lubricant;

(d) 5 - 10% of a taste masking agent; (e) 1 - 10% of a disintegrant; and (f) 2 - 25% of a binder. wherein the composition has a friability of less than 0.5% w/p and a hardness of greater than 80N.

[00112] More preferably, the composition may consist essentially of: (a) 28 - 30% of an uncoated NSAID having an average particle size of 50 µm or a pharmaceutically acceptable salt thereof; (b) 0.5 - 1.5% of a glidant; (c) 42 - 47% of a filler; (d) 0.75 - 1.5% of a lubricant; (e) 8 - 12% of a binder; (f) 6 - 8% of a taste masking agent; and (g) 3 - 5% of a disintegrant. wherein the composition has a friability of less than 0.5% w/p and a hardness of greater than 80N.

[00113] More preferably, the composition may consist essentially of: (a) 28 - 30% uncoated ibuprofen with an average particle size of 50 µm or a pharmaceutically acceptable salt thereof; (b) 0.5 - 1.5% of a colloidal silica; (c) 42-47% of a mannitol; (d) 0.75 - 1.5% of a sodium stearyl fumarate; (e) 8 - 12% of a microcrystalline cellulose; (f) 6 - 8% of a malic acid; and (g) 3 - 5% of a crospovidone,

wherein the composition has a friability of less than 0.5% w/p and a hardness of greater than 80N.

[00114] In another aspect of the present invention, there is provided the use of malic acid as a taste masking agent in a composition comprising uncoated ibuprofen having an average particle size of 40-60 µm. Preferably, the average particle size of the uncoated ibuprofen is 50 µm.

[00115] The weight ratio of uncoated ibuprofen and malic acid in the composition may be 1:1 - 8:1. A preferred ratio is 3:1 - 5:1. The most preferred ratio is 4:1 by weight.

[00116] Preferably, the present invention provides the use of malic acid as a taste masking agent in a composition comprising uncoated ibuprofen having an average particle size of 50 µm, wherein the weight ratio of the uncoated ibuprofen and malic acid is 4:1.

[00117] For the avoidance of doubt, the percentages expressed above are the percentages by weight of the composition.

[00118] For the avoidance of doubt, the term "uncoated" refers to ibuprofen prior to incorporation into the composition. The ibuprofen particles of the present invention are mixed with the silica so that there is a mixture between the ibuprofen and the silica rather than any modification of the surface of the ibuprofen by the silica.

[00119] For the avoidance of doubt, the term "average particle size" refers to the average particle size of the ibuprofen used in the composition. For example, an average particle size of 50 µm means that ibuprofen has an average particle size of 50 µm.

[00120] The ibuprofen particles of the present invention are mixed with the silica so that there is a mixture between the ibuprofen and the silica rather than any modification of the surface of the ibuprofen by the silica.

[00121] For the avoidance of doubt, the term "orodispersible tablet", as used in the present specification, refers to a solid single dose preparation consisting of an uncoated tablet which is placed in the moth where it disperses rapidly in saliva before be swallowed.

BRIEF DESCRIPTION OF THE DRAWINGS

[00122] Embodiments of the present invention will now be described, by way of example only, with reference to the accompanying Figures in which:

[00123] Figure 1 illustrates dissolution data for compositions of the present invention and the prior art.

DETAILED DESCRIPTION OF THE INVENTION Examples Component Example 1 (% by wt) Example 2 (% by wt) Ibuprofen 28.57 28.57 Colloidal Silica 1.00 1.00 Mannitol 45.63 44.18 Cellulose 10.00 10.00 microcrystalline Crospovidone 4 .00 4.00 Malic Acid 7.14 7.14

Component Example 1 (% by wt) Example 2 (% by wt) Fumarate 1.25 1.25 Sodium Stearyl Sucralose 0.86 0.86 Flavor 1.55 3.00 TOTAL 100.00 100.00

[00124] The orodispersible tablet can be prepared by a process involving dry mixing or wet or dry granulation. However, it is preferred to use a manufacturing method which involves direct compression into an orodispersible tablet without an intermediate, e.g. a wet or dry granulation stage.

[00125] The composition can be made by dry mixing the active ingredient with one or more of the other ingredients, e.g. e., the lubricant and diluents and disintegrants, e.g. e., in a powder mixing machine. The active agent can be mixed with the silica. The remaining ingredients can be mixed separately. The two mixtures can then be combined. It is particularly preferred that the active ingredients are dispersed by progressive dilution with stirring in a proportion, e.g. e., about half of the excipients in order to achieve an even distribution of the active ingredient in the excipients, and then add the remainder of the excipients with additional stirring and mixing. The mixture can then be compressed in a tabletting machine.

[00126] The flavor and mouthfeel characteristics of the compositions were evaluated. Participants in evaluating the compositions of the present invention received 2 tablets - the first was an orodispersible tablet according to the present invention and the second was a sample of a commercially available orodispersible tablet.

[00127] Participants sampled each orodispersible tablet and recorded their observations for each characteristic, giving a rating of 10. Participants were given mouthwash water between sampling each orodispersible tablet.

[00128] The table below illustrates the average rating of 10 participants who compared orodispersible tablets. Characteristic Example of the Example of the present invention comparative (Ave) (Ave) Acceptability of 7.5 6.7 mouthfeel Acceptability of 6.8 5.6 texture Taste acceptability 7.7 6.7 Acceptability of 6.9 6.2 duration in the mouth Overall rating 7.2 6.6

[00129] As can be seen, the composition of the present invention received a significantly higher rating than the comparative example by the panelists.

[00130] Figure 1 illustrates the dissolution profile for a composition of the present invention and an orodispersible tablet that is currently available. As can be seen, the dissolution of ibuprofen in the orodispersible tablets of the present invention is significantly faster than that of a comparable existing tablet.

[00131] The dissolution of ibuprofen was measured using a pH shift dissolution method. The pH shift method uses a standard Ph Eur rowing apparatus and UV detection. This method is designed to more accurately reflect the change in pH that occurs between the stomach and intestine and provide a more bio-relevant comparison for the products. A composition of the present invention and a currently commercially available orodispersible tablet are subjected to 9.5 minutes of dissolution in 500 mL of pH 1.2 (using 0.1 M HCL) and then 400 mL of a buffer solution is added. concentrated. Dissolution is continued to the defined end point (this final solution has a pH between 6-8). The amount of dissolved ibuprofen is measured by UV absorbance every 5 minutes up to 90 minutes.

[00132] Hardness and friability were measured using the relevant European Pharmacopoeia methods as described in sections 2.9.8 and 2.9.7, respectively.

[00133] An advantage of the present invention is that an orodispersible tablet is provided which comprises an uncoated ibuprofen particle and has a good organoleptic profile with effective taste masking, disintegrates in the mouth in less than one minute. As can be seen in Figure 1, the use of an uncoated ibuprofen particle results in a significantly better dissolution profile than the dissolution profile of a product comprising a coated ibuprofen.

[00134] The present invention is not intended to be limited to the exemplary embodiments described herein.

Other modifications can be made without departing from the scope of the invention described herein.

Claims (40)

1. A composition in the form of an orodispersible tablet characterized in that it comprises a non-steroidal anti-inflammatory drug (NSAID) and a taste masking agent, wherein the NSAID is uncoated and has an average particle size of less than 100 µm. 2. Composition according to claim 1, characterized in that the average particle size of the uncoated NSAID is 40 - 60 µm. 3. Composition according to claim 2, characterized in that the average particle size is 50 µm. 4. Composition according to any one of claims 1 to 3, characterized in that the NSAID is ibuprofen and its pharmaceutically acceptable salts or hydrates. 5. Composition according to any one of claims 1 to 4, characterized in that the taste masking agent is selected from the group consisting of ascorbic acid, monosodium citrate, fumaric acid, malic acid and combinations thereof. 6. Composition according to claim 5, characterized in that the flavor masking agent is malic acid. 7. Composition according to claim 5 or 6, characterized in that the amount of taste masking agent is 0.1 - 15% by weight of the composition. 8. Composition according to claim 7, characterized in that the amount of malic acid is from 5 to 10% by weight. 9. Composition according to claim 7 or 8, characterized in that the amount of malic acid is from 7 to 9% by weight. 10. Composition according to any one of claims 1 to 9, characterized in that the weight ratio of the non-steroidal anti-inflammatory drug (NSAID) and the taste masking agent in the composition can be 1:1 - 8:1. 11. Composition according to claim 10, characterized in that the ratio of NSAID and taste masking agent is 3:1 - 5:1. 12. Composition according to claim 11, characterized in that the ratio of the NSAID and the taste masking agent is 4:1 by weight. Composition according to any one of claims 1 to 12, characterized in that the composition includes a mixture of a cellulosic binder, a sugar alcohol filler and a disintegrant. 14. Composition according to claim 13, characterized in that the cellulosic binder is microcrystalline cellulose, the sugar alcohol is mannitol and the disintegrant is cross-linked polyvinylpyrrolidone (crospovidone). Composition according to any one of claims 13 or 14, characterized in that the composition contains 2 - 4 parts by weight of cellulosic binder per part by weight of disintegrant and 8 - 12 parts by weight of alcohol binder of sugar per part by weight of disintegrant. 16. Composition according to claim 15, characterized in that the composition contains cellulosic binder, sugar alcohol filler and disintegrant in a weight ratio of about 2 - 3:11 - 12:1. 17. Composition according to any one of claims 1 to 16, characterized in that the composition has a friability of up to 2% w/p and a hardness between 40N and 100N. 18. Composition according to claim 17, characterized in that the composition has a friability of less than 1% w/p and a hardness of more than 50N. 19. Composition according to claim 17 or 18, characterized in that the composition has a friability of less than 0.5% w/w and a hardness greater than 80N. 20. A composition according to any one of claims 1 to 19, characterized in that the composition comprises an uncoated non-steroidal anti-inflammatory drug (NSAID), a taste masking agent and a disintegrant, wherein the NSAID uncoated has an average particle size of less than 100 µm, the taste masking agent is selected to be malic acid which is present in an amount of 0.1 - 15% by weight of the composition, and the disintegrant is selected to be cross-linked polyvinylpyrrolidone (crospovidone) which is present in an amount of 1-10% by weight of the composition. 21. A composition according to any one of claims 1 to 19, characterized in that the composition comprises an uncoated non-steroidal anti-inflammatory drug (NSAID), a taste masking agent and a disintegrant, wherein the NSAID uncoated has an average particle size of less than 100 µm, the taste masking agent is selected to be malic acid which is present in an amount of 0.1 - 15% by weight of the composition, wherein the proportion of anti-cancer drug -uncoated non-steroidal inflammatory (NSAID) to taste masking agent is 4:1 by weight. Composition according to claim 19, characterized in that the composition further comprises a disintegrant which is selected to be cross-linked polyvinylpyrrolidone (crospovidone) and which is present in an amount of 1 - 10% by weight of the composition. 23. Composition according to any one of claims 1 to 22, characterized in that the composition comprises ibuprofen, a taste masking agent and a disintegrant, wherein the weight ratio of ibuprofen: taste masking agent: disintegrant is from about 10:5:1 to about 5:1:1. 24. Composition according to claim 23, characterized in that the weight ratio of ibuprofen: taste masking agent: disintegrant is from about 8:2:1 to about 7:1:1. A composition according to any one of claims 1 to 24, wherein the composition comprises uncoated ibuprofen, a taste masking agent and a disintegrant, wherein the uncoated ibuprofen has an average particle size of 50 µm, the taste masking agent is selected to be malic acid which may be present in an amount of 7 - 9% by weight of the composition, wherein the ratio of uncoated ibuprofen to taste masking agent is 4: 1 by weight and the disintegrant is selected to be cross-linked polyvinylpyrrolidone (crospovidone) which may be present in an amount of 3 to 6% by weight of the composition and wherein the weight ratio of ibuprofen: taste masking agent: disintegrant is about 8:2:1 to about 7:1:1. 26. Composition according to any one of claims 1 to 25, characterized in that the composition comprises an uncoated non-steroidal anti-inflammatory drug (NSAID), a taste masking agent, a binder, a disintegrant and a filler, wherein the uncoated NSAID has an average particle size of less than 100 µm, the taste masking agent may be present in an amount of 0.1 - 15% by weight of the composition, wherein the ratio of the NSAID to taste masking agent is 4:1 by weight and wherein the composition contains 2 to 4 parts by weight of binder per part by weight of disintegrant and 8 to 12 parts by weight of filler per part by weight of disintegrant. A composition according to claim 26, characterized in that the composition is in the form of an orodispersible tablet comprising uncoated ibuprofen, a taste masking agent, a cellulosic binder, a disintegrant and an alcohol filler. of sugar, wherein the ibuprofen has an average particle size of 50 µm, the taste masking agent is selected to be malic acid and is present in an amount of 0.1 - 15% by weight of the composition, wherein the ratio of the uncoated ibuprofen to the taste masking agent is 4:1 by weight, the cellulosic binder is selected to be microcrystalline cellulose and is present in an amount of 2 to 25% by weight of the composition, the disintegrant is selected for be cross-linked polyvinylpyrrolidone (crospovidone) and is present in an amount of 1-10% by weight of the composition, the filler is selected to be mannitol and is present in an amount of 20 to 70% by weight of the composition. composition, wherein the composition contains 2 to 4 parts by weight of cellulosic binder per part by weight of disintegrant and 8 - 12 parts by weight of sugar alcohol filler per part by weight of disintegrant, and wherein the weight ratio of ibuprofen: malic acid: cross-linked polyvinylpyrrolidone is from about 10:5:1 to about 5:1:1. A composition according to any one of claims 1 to 19, characterized in that the composition comprises: (a) 20 - 35% of an uncoated NSAID with an average particle size of less than 100 µm or a pharmaceutically acceptable thereof; (b) 20 - 70% of a filler; (c) 0.5 - 5% of a lubricant; (d) 5 - 10% of a taste masking agent; and (e) 1 - 10% of a disintegrant. A composition according to claim 28, characterized in that the composition comprises: (a) 25 - 30% of an uncoated NSAID with an average particle size of less than 100 µm or a pharmaceutically acceptable salt thereof; (b) 40 - 50% of a filler; (c) 0.5 - 5% of a lubricant; (d) 5 - 10% of a taste masking agent; and (e) 1 - 10% of a disintegrant. 30. Composition according to claim 28 or 29, characterized in that the composition further comprises one or more additional excipients selected from: (f) 0.1 - 5% of a glidant; and (g) 2 - 25% of a binder. A composition according to any one of claims 28 to 30, characterized in that the composition further comprises: (a) 28 - 30% of an uncoated NSAID with an average particle size of less than 100 µm or a salt pharmaceutically acceptable thereof; (b) 0.5 - 1.5% of a glidant; (c) 42 - 47% of a filler; (d) 0.75 - 1.5% of a lubricant; (e) 8 - 12% of a binder; (f) 6 - 8% of a taste masking agent; and (g) 3 - 5% of a disintegrant. A composition according to any one of claims 28 to 31, characterized in that the composition comprises: (a) 25 - 30% uncoated ibuprofen with an average particle size of less than 100 µm or a pharmaceutically acceptable salt the same; (b) 0.1 - 5% colloidal silica; (c) 40 - 50% mannitol; (d) 0.5 - 5% sodium stearyl fumarate; (e) 5 - 15% microcrystalline cellulose; (f) 5 - 10% malic acid; and (g) 1 - 10% crospovidone. A composition according to any one of claims 28 to 32, characterized in that the composition comprises: (a) 28 - 30% uncoated ibuprofen with an average particle size of less than 100 µm or a pharmaceutically acceptable salt the same; (b) 0.5 - 1.5% colloidal silica; (c) 42 - 47% mannitol; (d) 0.75 - 1.5% sodium stearyl fumarate; (e) 8 - 12% microcrystalline cellulose; (f) 6 - 8% malic acid; and (g) 3 - 5% Crospovidone. 34. Composition according to any one of claims 28 to 33, characterized in that the average particle size of uncoated ibuprofen is 40 to 60 µm. 35. Use of malic acid characterized in that it is as a taste masking agent in a composition in the form of an orodispersible tablet comprising an uncoated ibuprofen particle with an average particle size of 40 - 60 µm. 36. Use according to claim 35, characterized in that the average particle size of uncoated ibuprofen is 50 µm. 37. Use according to claim 35 or 36, characterized in that the weight ratio of uncoated ibuprofen particle and malic acid in the composition is 1:1 - 8:1. 38. Use according to claim 37, characterized in that the weight ratio of uncoated ibuprofen particle and malic acid in the composition is 3:1 - 5:1. 39. Use according to claim 38, characterized in that the weight ratio of the uncoated ibuprofen particle and malic acid in the composition is 4:1. 40. Use of malic acid characterized in that it is as a taste masking agent in a composition in the form of an orodispersible tablet comprising an uncoated ibuprofen particle having an average particle size of 50 µm, wherein the ratio by weight of the uncoated ibuprofen particle and malic acid is 4:1.